FDA Puts the Kibosh on Fluoroquinolones – So Should You

The latest “black box” warning focuses on an array of neurological problems associated with these antibiotics.

For emergency clinicians, the fluoroquinolone antibiotics have been a staple in combating both outpatient and inpatient infections. The first fluoroquinolone (ciprofloxacin/Cipro) came on the market in 1987, and since then there have been a raft of new quinolones added to the drug class. The fluoroquinolones have been shown to have a wide spectrum of biologic activity and are effective against a large number of bacteria pathogens.

That’s the good news. But post-marketing surveillance has demonstrated a growing number of serious and unexpected side effects. Perhaps the most commonly known unique side effect of the quinolones relate to their effect on connective tissue – particularly in the Achilles tendons. The relationship between tendon pathology and the quinolones was noted back in 1983, but the FDA was very reluctant to “Black Box” the drugs until a lawsuit filed by the non-profit “Public Citizen” pressured the FDA to acknowledge the problem. In the end the boxed warning took 25 years to appear, finally surfacing in 2008.

The first lawsuit regarding tendon rupture occurred in 2010 when a Minnesota jury awarded $1.8 million to 82-year-old John Schedin who had bilateral achilles ruptures after being given levofloxacin for a respiratory infection along with some steroids by his family doctor. The case was the first of about 2,600 similar lawsuits.

In the Schedin case the majority of the award ($1.1 million) was for punitive damages against Johnson & Johnson because it was believed that the company recklessly failed to warn consumers and physicians about the risk of tendon injuries.

But the Schedin case and the associated Black Box are old news now. Every prescriber should know that tendon problems can occur with the quinolones, and it would seem logical that they be avoided when there are other safer alternative antibiotics (which there usually are). Here are some additional tidbits regarding tendon-related problems associated with the quinolones:

But given the seriousness of the latest Black Box on the fluoroquinolones, tendon rupture appears like a hiccup in comparison. More specifically, the newest Black Box on these antibiotics came out on May 16, 2016 and focused on an array of neurologic problems. Through post-marketing surveillance it was noted that a variety of psychiatric and neurologic problems were disproportionately happening in association with fluoroquinolone use. In fact, here’s an abstract from the Emergency Medical Abstracts database that specifically addresses the issue, and was published in 2011 – fully five years before the Black Box warning was issued. Some of the key points from the paper:

The incidence of psychiatric and neurologic side effects is estimated at 1-2%. That sounds very high, however how many patients taking these medications had trouble sleeping while on them or felt a little “up tight” and never considered the drugs to be the cause? And how many patients presented to their clinicians with a variety of neurologic or psychiatric symptoms while on the drugs that were dismissed as unrelated because no one has ever heard of an antibiotic causing such problems?

About half the patients in the series had psychiatric effects and the other, neurologic symptoms.

The most common neurologic effects were seizures, confusion, headaches, dizziness tremors and myoclonus, while the most common psychiatric effects were mania, insomnia, psychosis anxiety, hallucinations paranoia, and delirium (suicide attempts have been reported at high doses).

Symptoms were noted from hours to weeks after taking the antibiotic and averaged 14 months in duration (as long as nine years has been reported).

RESULTS: Nearly half of the reports involved ciprofloxacin, and nearly one-fourth involved use of ofloxacin. Adverse CNS events were considerably less common with levofloxacin. The authors suggest that widespread use of ciprofloxacin worldwide might account for overrepresentation of this agent in adverse event reporting. Just over half of the events (53.9%) involved psychiatric disorders, most commonly including mania, insomnia, acute psychosis, and delirium. Neurological events accounted for the remainder of the adverse CNS occurrences, most commonly including seizures, confusion, and myoclonus. Adverse CNS events generally developed within minutes to days after starting treatment. Some events might have been precipitated by concomitant treatment with a quinolone and theophylline, nonsteroidal antiinflammatory drugs or, less commonly, other agents (e.g., antivirals, antihistamines, antidepressants, and opioid analgesics). Because theophylline concentrations are increased, and clearance decreased, in the setting of quinolone treatment, a reduced theophylline dose is advised in this circumstance. Other factors that might contribute to the development of adverse CNS events with quinolone treatment include a history of seizures, electrolyte disturbances, renal and/or hepatic failure, older age, and excessive dosing. Dose adjustment is advised in patients with comorbidity.

CONCLUSIONS: Clinicians should be aware of the potential for, and possible precipitants of, adverse CNS events with quinolone therapy.

So here’s what the FDA says about its new warning (underlining added):

“The U.S. Food and Drug Administration (FDA) approved changes to the labels of fluoroquinolone antibacterial drugs for systemic use (i.e., taken by mouth or by injection). These medicines are associated with disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system that can occur together in the same patient. As a result, we revised the Boxed Warning, FDA’s strongest warning, to address these serious safety issues. We also added a new warning and updated other parts of the drug label, including the patient Medication Guide.”

… “Health care professionals should not prescribe systemic fluoroquinolones to patients who have other treatment options for acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI) because the risks outweigh the benefits in these patients. Stop fluoroquinolone treatment immediately if a patient reports serious side effects, and switch to a non-fluoroquinolone antibacterial drug to complete the patient’s treatment course.”

The lay public has dubbed the fluoroquinolone-related condition as “floxing,” and the verb “floxed” has been created. To get some sense of the extent of the neurologic problems, merely go onto the internet and check out the many stories of patients with a wide variety of symptoms, both musculoskeletal and neuropsychiatric that are being attributed to the fluoroquinolones. A story written in Forbes by Melanie Haiken on this subject received over 70 comments and had almost 150,000 views. Check out FloxieHope.com, FQWallofPain.com, and rxisk.org/flox-tox-guerilla-guide.

Bottom line –Don’t prescribe fluoroquinolones unless they are absolutely needed and there are no good alternatives (and there usually are at least a few). It will be very difficult to defend your practice if a patient is seriously harmed, as there was an FDA Black Box about the side effect caused, and there were other alternatives. It is surprising that more hospitals haven’t responded to this new Black Box despite the medicolegal risks they may incur by not warning their medical staffs about the use of these drugs. Compare the response to the current fluoroquinolone Black Box with the exaggerated response to the Black Box on droperidol regarding arrhythmias. Most hospitals quickly made droperidol unavailable while nothing similar has occurred regarding the quinolones.

Tell Your Story

Email editor@epmonthly.com and tell us how your hospital has handled the quinolone black box warnings.

12 Comments

Sadly, those new warnings from the FDA were never given directly to doctors via some sort of official FDA communication. The new warnings also fail to include mitochondrial toxicity and to make is beyond clear that there is a whole constellations of symptoms that have the very real possibility of becoming permanent and that most symptoms do NOT go away (and some do not even start) until after the patient has stopped taking the drug.

Sadly, so many providers are still harming people. I meet them each and every day.

Thank you Dr. Bukata for this important piece warning about the misuse of all FQA in non life threatening conditions. I am personally not a doctor but have 3 family members in different fields of medicine and they are all implementing change slowly. I have been told that doctors have alarm fatigue and also do not want to lose this easy tool for infections. If the medical profession could only begin to see the under-recognized side effects they would surely not be prescribing this class of antibiotics. It is so hard to see side effects that occur 6 months after a prescription and understand that they can disable anyone at any age. I was in perfect health and given Levaquin for suspected pneumonia. I had been mountaineering the day before and my life was certainly not threatened. Within a week I started to become disabled and went downhill for a year. I had to use crutches to walk for over 2 years. My doctors attribute all of my disabling symptoms to Levaquin and have changed their practice. I testified at the FDA to help prompt new stronger warnings. Yes I am glad the warnings are stronger but in the Boston area the medical world is not heeding the warnings. I meet someone weekly damaged…..traced with their doctor. Please keep spreading the word. The NYT has articles often on the uptick of joint replacements, disabling joint problems and nerve damage. Could this be a result from over use of FQA. At least a co-factor I am sure. Thanks again!

I’ve been floxed 6 months ago. The doctor prescribed me levofloxacin for a sinus infection (turns out it was viral). I started feeling symptoms hours after the first dose. In the second dose my body just exploded and it was the worst experience in my whole 30 years of life. Until today I performed more than 30 blood exams, 5 MRI’s, 3 brains tests and there’s nothing possible to help me. I have a chronic fatigue, 4 tendons that are about to rupture, headaches, insomnia, arrhythmia, Tietze syndrome, fibromyalgia, collagen related problems, paranoia, depression, cracking joints and much more. This is being a true nightmare. Everyday I struggle to just exist. I’m not against the use of FQ’s in case of life and death situations, but taking it for a simple sinus infection it’s pure madness. I wish I have done a quick research about this pill before taking it. 2 pills and my life is runied.

Hang in there!! I took one pill in January this year for supposed sinus infection and possible pneumonia and I’m just now getting better!! I didn’t think it would happen. I kept trying to move around and it was always a disaster. The best advice I can give you is to REST and let your body heal on its own. This situation I not like any other and literally doing nothing is what I needed. Don’t take anything for this besides pain medicine to get through hellish hellish pain. But don’t do ibuprofen or steriods. It will make it worse. You’ll have less range of motion too that can be permanent. Don’t do physical therapy it will make it worse. Just move around as you can. Now this will sound crazy… but eat as much fruit and citrus as you can! I promise it helps. I was in a wheel chair and I’m finally moving around without wishing I was dead. It will get better it just takes a really really long time! Listen to your body and your instincts. Forget the doctors they don’t know what to do with us!!! God bless you. He will heal you!! 🙂

I was given cipro in 2009 during chemo and kept telling my Dr. I had major pain in my right knee he refused to take me off it I was doing 1,000 mg a day for 60 days. The pain was so bad I could not walk then I fell down a flight of stairs after my knee gave out and tore my shoulder. I now have so many health problems including nerve damage . I can’t get any Dr. to look at the side effect and what I’m going through

I went to the ER in February of 2017 with chest pain. They did xray and ct scan, blood work and a few other tests. Couldn’t find anything wrong with me. The dr came in and said “I think you’re getting the flu, did they swab you?”
No they didn’t. “Well take this antibiotic and you will be fine.”
She prescribed me Levaquin. Once a day for 5 days. On day 2 I couldn’t get out of bed. I had tendinitis in every joint. My knees felt like they were going to explode every time I sat down. I went back to the ER and was admitted to the hospital. My tendons were on the verge of rupture. They kept me 3 days, with strict instructions not to run, jump, throw or lift anything. I was sent home unable to walk, couldn’t pick up my 5 month old twins.
My joints still ache, my elbows are swollen all the time. My feet hurt constantly. I still run the risk of tendon rupture. I haven’t been able to go back to work.

I was given cipro 5 years ago. it destroyed my tendons and I’m in pain every day. drug companies are absolutely protected because of the black box warning, so I get to deal with the ruins of my body and my life and there are no consequences for those who manufactured this poison and covered up the true extent of the risks.

I took a lifesaving systemic dose of Cipro in 1990 when I was fighting for my life against a cellulitis infection that would have taken my leg at best and my life at worst without it.

Now, 27 years later, I am unsure what of my challenges have been related to this medication, but I do often wonder. I have Celiac disease and chronic fatigue, onset at about 40. I struggle with irrational pain throughout my body most of the time. I am thankful to be alive but I wonder to what extent my microbiome paid the price and I have been unable to resurrect it. I hope the connection between These medications and the microbiome will be considered.

I took Amoxicillian off and on from Jan 2010 til July 14, 2010 for upper respiratory infection. July 14. 2010 I was given Leaviquin for 10 days. The 2nd day after taking it I was experiencing leg pain. I called my Dr. and said “oh keep taking it, it will pass”. Of course I did but it never passes. I went in to see my Dr. about 2 weeks later and I was in pain and acted like there was nothing wrong with me. My husband got up in his face and said you have to find out what is going on. Finally my Dr. said Ok, we will do blood work. We went down to the lab for blood work and then went home. At 7:00 the next morning, my phone was ringing a lot. I finally got the phone and it was my Dr. telling me to get to a neurologist right a way. He was going to refer me and I said no! I have an internist that I will go see. I went to see my internist the next day and he to,d me he believed that I had developed Polymyositis. He said I had to go to Baylor Colkege of Medicine and see Dr. Hurati who was over the Neurology department. I went to see Dr. Hurati and he said he believed I developed a Myositis. He told me that there were 5 types and that if he chose one and treated me for it and it was not the correct one that it could be very detrimental for me. So he said I had to have a muscle biopsy done to determine which one I had. So he sent over to a surgeon who did a muscle biopsy. The muscle biopsy showed I had Polimyositus. The Nuerologist had me going over toBaylor evetyday for acweek for IV treatmeny trying to slow down the progression. By December 2010 my family was told to make funeral arrangements. My throat had closed, I was on a feeding tube and a line that went to my heart for meds. The oncologist saved my life. I spent nearly 5 months in hopital/rehab. Once my throat started to open, I had to learn how to swallow and eat, it was painful and a slow process. I also had to learn how to talk again. I came home and had occupation and physical therapy for 3 years. I had a nurse that would come 2 tomes a week to check me. I had to learn how to walk again and use my hands and full body. By the end of 3 years I was walking with a walker. I started having stomach pain. Had to have emergency surgery to have gallbladder removed. My body went down hill again. My famly again was told to make funeral arrangements. I made it. Again a feeding tube and had to redo everything I did the first time. Its now been 2 1/2 years since the gallbladder issue and now I am bed bound. My feet are turned in and my left hand is turned in. I worked in Mortgage Bankng 36 years, that drug almost cost me my life twice. It cost me my livelthoid as I knew it and I dearly miss it.

Thanks so much for this article. Fortunately I am a part of the July 2016 warnings. I sent in written testimony to the FDA and while reviewing the November 5, 2015 documents, found my case was included in the samples provided to the panel. It was a long hard fought battle to get the FDA to update these warnings.
Like many of us, I had a total of seven (7) tendon tears which resulted in surgery. I was given Levaquin and Avelox over and over again starting in 2001 to 2011 the year I learned what had caused all the tendon tears.
And that was not the end. I developed Ulcerative Colitis in 2011 placed on a lot of prednisone along with lialda and eventually developed Osteonecrosis (AVN) of my right hip resulting in hip replacement at the age of 54. An example of how far reaching the damage by these drugs can be.
To this day I live with small fiber neuropathy. I have good days and bad days but the SFN will most likely never go away.
Instead of becoming a victim, I became an advocate for drug safety and change. And my work along with thousands of others resulted in these increased box warnings. My question is what will it take to get these unsafe drugs pulled from the market. Since when do benefits outweigh the risks. And most importantly, what can be done to inform the doctors? It’s a monumental task that I believe the drug manufacturers are responsible for.
The end result of all this, and you will not find this side effect on any drug label, is the medical industry destroyed trust. I can no longer trust doctors, no matter how hard I try. I will never trust the pharmaceutical industry, they’ve done more damage than the 22 years I spent in the Army. Greed has consumed our medical professions and destroyed the integrity of those that work in the field. It’s something that no doctor, nurse, etc., will ever be able to regain from me. I have lost faith in medical science, and greed is to blame.

As a victim myself of several different Fluoroquinolone drugs from the 90s, INCLUDING the ear solution in 2013, which by the way doctors and the FDA feel topicals do NO harm, I feel the new labeling of this class of drugs is NOT for the patient BUT for the drug companies who are covering their a…… just in case they are sued. If it’s on the label, we were warned. The problem is the doctors are NOT warning us and still continue to give them out like candy. My father died 6 weeks after given IV Levaquin for pneumonia he never had. He hallucinated for those 6 weeks and then his aortic aneurysm ruptured. I spoke at the big FDA meeting regarding these poisons and the doctors sitting there listening to our stories were aghast, which surprises me because there were already black box warnings from 2008.

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